Absence of late airway response despite increased airway responsiveness and eosinophilia in a murine model of asthma

In asthmatics an immediate asthmatic response occurs after antigen provocat ion. Furthermore, asthmatic patients display airway hyperresponsiveness, ac companied by airway eosinophilia. In some patients late asthmatic responses can be detected. Many controversies still exist about the relations betwee n the different airway responses and inflammatory cell infiltration, we the refore used a murine model to investigate associations between these phenom ena. In this study we show the presence of antigen-induced early bronchocon strictive responses, accompanied by increased serum mucosal mast cell prote ase-1 (MMCP-1) levels. However, we were unable to demonstrate late bronchoc onstrictive responses either at the time when eosinophils start to infiltra te the lungs or when both airway hyperresponsiveness and eosinophilia are e stablished. With sequential exposures to antigen, an association exists bet ween development of airway hyperresponsiveness and eosinophilia. In contras t, resolution of this hyperreactivity appears to be dissociated from eosino philia after stopping the antigen challenges. Based on these data, we concl ude that mast cell degranulation is a plausible cause of early bronchoconst rictive responses. Furthermore, late bronchoconstrictive responses are not related to the infiltration of eosinophils or development of airway hyperre sponsiveness in this murine model. Finally, we conclude that airway hyperre sponsiveness and eosinophilia are only associated with each other during th e induction phase and not after the final antigen challenge.